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Open Heart May 2024Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost.
OBJECTIVE
We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies.
METHODS
Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label.
RESULTS
Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: -0.44 (95% CI -0.49 to -0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy.
CONCLUSIONS
Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.
Topics: Female; Humans; Heart Failure; Stroke Volume; Treatment Outcome; Trimetazidine; Vasodilator Agents; Ventricular Function, Left
PubMed: 38719498
DOI: 10.1136/openhrt-2023-002579 -
BMC Complementary Medicine and Therapies May 2024Pragmatic acupuncture trials (PATs) are a research tool for assessing the effectiveness of acupuncture treatments in a real-world setting. This study aimed to provide a...
BACKGROUND
Pragmatic acupuncture trials (PATs) are a research tool for assessing the effectiveness of acupuncture treatments in a real-world setting. This study aimed to provide a comprehensive methodological analysis of PATs using the PRECIS-2(PRagmatic Explanatory Continuum Indicator Summary-2) tool to determine their pragmatism.
METHODS
The MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials, CINAHL, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, VIP, WANFANG, Taiwan Periodical Literature Database, KoreaMed, KMbase, Research Information Service System, Oriental Medicine Advanced Searching Integrated System, CiNii and ClinicalTrials.gov were searched. The search included randomised controlled trials (RCTs) and protocols of RCTs that investigated all types of acupuncture and used self-declared pragmatic design. Two authors independently collected the basic information and characteristics of the studies and assessed their pragmatism using the nine PRECIS-2 domains and the additional domain of control.
RESULTS
A total of 93 studies were included. The means of eligibility, recruitment, organisation, primary outcome, primary analysis, and control domains were statistically larger than three and were shown to be pragmatic. The means of setting, flexibility:delivery, and follow-up domains were not greater than three and were shown to be non-pragmatic. For flexibility:adherence domain was inappropriate for assessment owing to insufficient information in the studies.
CONCLUSIONS
PATs were pragmatic in the domain of eligibility, recruitment, organisation, primary outcome, primary analysis, and control and were not pragmatic in the domain of setting, flexibility:delivery, and follow-up. Future PATs need to strengthen the pragmatism in the setting, flexibility:delivery, and follow-up domains and to describe the flexibility:adherence domain in more detail.
TRIAL REGISTRATION
CRD42021236975.
Topics: Humans; Acupuncture Therapy; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design
PubMed: 38702632
DOI: 10.1186/s12906-024-04473-7 -
The Journal of the American Academy of... Apr 2024Depression is a notable contributor to suboptimal outcomes after total joint arthroplasty (TJA). We conducted a systematic review of comparative studies to review the...
PURPOSE
Depression is a notable contributor to suboptimal outcomes after total joint arthroplasty (TJA). We conducted a systematic review of comparative studies to review the available evidence of interventions that affected depression scores and/or outcomes for patients undergoing TJA.
METHODS
EMBASE, Ovid MEDLINE, PubMed, and Scopus were reviewed systematically from inception until November 15, 2022. Studies that were relevant for this review included comparative studies between patients who received an intervention within 3 months before or after their primary total hip or knee arthroplasty procedure. The interventions included a wide range of modalities, which were grouped into psychotherapy, enhanced perioperative support, and pharmacotherapy. Other interventions included physiotherapy techniques with a psychological focus, art/music-based therapy, occupational therapy support, and educational interventions. Meta-analysis was conducted for psychotherapy and enhanced support.
RESULTS
The final systematic review consisted of 28 relevant studies, most of which were randomized controlled trials. A total of 3,702 patients, with a mean age of 66 years, were considered, of whom 59% were female. Most of the studies reported a notable reduction in depressive symptoms and/or scores based on the interventions being analyzed. At 3 months postoperatively, psychotherapy and enhanced support both resulted in markedly better depression and function scores compared with control subjects, with psychotherapy additionally improving pain scores.
CONCLUSIONS
Overall, a wide range of interventions aimed at psychological optimization of patients undergoing TJA can improve depressive symptoms, pain, and function, even in the absence of a formal diagnosis of depression. Specifically, cognitive-based psychotherapy and enhanced perioperative support had the best evidence. Routine pharmacotherapy plays a limited role, if any, in the care of TJA. Additional efforts to develop pragmatic, evidence-based, and reproducible interventions are warranted to continue to optimize outcomes in TJA patients.
PubMed: 38626430
DOI: 10.5435/JAAOS-D-23-01130 -
The Journal of Manual & Manipulative... Mar 2024Disorders of the cervical spine are some of the costliest musculoskeletal conditions to manage globally. Joint mobilization and manipulation have been shown to be an... (Review)
Review
BACKGROUND
Disorders of the cervical spine are some of the costliest musculoskeletal conditions to manage globally. Joint mobilization and manipulation have been shown to be an effective treatment for neck pain. However, the generalizability and clinical translation depends on the nature of the trial designs that inform its use. The extent to which randomized control trials (RCTs) assessing manual therapy treatments for cervical spine disorders fall on the efficacy (explanatory) -effectiveness (pragmatic) spectrum often informs how the findings are translated into clinical practice.
OBJECTIVE
The aim of this systematic review was to determine where RCTs of manual therapy for neck disorders fall on the efficacy-effectiveness spectrum.
METHODS
A search of three electronic databases including PubMed, CINAHL, and CENTRAL were completed for trials published from inception to May 2023. RCTs in which joint mobilization or manipulation were used to treat cervical spine disorders were assessed on the effectiveness-efficacy spectrum using the Rating of Included Trials on the Efficacy-Effectiveness Spectrum (RITES) tool and risk of bias using the Revised Cochrane Risk of Bias tool.
RESULTS
A total of 174 trials met eligibility. RITES domain two trial setting (71.3% vs 16.1%), domain three flexibility of intervention(s) (62.1% vs 23%), and domain four clinical relevance of experimental and comparison intervention(s) (51.7% vs 29.3%) all favored efficacy over effectiveness. Domain one participant characteristic(s) had a slightly greater emphasis on effectiveness compared to efficacy (36.8% vs 44.8%). Most studies (96%) had at least some risk of bias.
CONCLUSION
Over half of the RCTs assessing the treatment effect of joint mobilization and manipulation for neck pain favor efficacy (explanatory) over effectiveness (pragmatic) designs. Future RCTs on this topic should consider a greater emphasis on pragmatic trial design components in order to better reflect real-world translation to clinical practice.
PubMed: 38525785
DOI: 10.1080/10669817.2024.2327127 -
JAMA Network Open Mar 2024Platform trials have become increasingly common, and evidence is needed to determine how this trial design is actually applied in current research practice.
IMPORTANCE
Platform trials have become increasingly common, and evidence is needed to determine how this trial design is actually applied in current research practice.
OBJECTIVE
To determine the characteristics, progression, and output of randomized platform trials.
EVIDENCE REVIEW
In this systematic review of randomized platform trials, Medline, Embase, Scopus, trial registries, gray literature, and preprint servers were searched, and citation tracking was performed in July 2022. Investigators were contacted in February 2023 to confirm data accuracy and to provide updated information on the status of platform trial arms. Randomized platform trials were eligible if they explicitly planned to add or drop arms. Data were extracted in duplicate from protocols, publications, websites, and registry entries. For each platform trial, design features such as the use of a common control arm, use of nonconcurrent control data, statistical framework, adjustment for multiplicity, and use of additional adaptive design features were collected. Progression and output of each platform trial were determined by the recruitment status of individual arms, the number of arms added or dropped, and the availability of results for each intervention arm.
FINDINGS
The search identified 127 randomized platform trials with a total of 823 arms; most trials were conducted in the field of oncology (57 [44.9%]) and COVID-19 (45 [35.4%]). After a more than twofold increase in the initiation of new platform trials at the beginning of the COVID-19 pandemic, the number of platform trials has since declined. Platform trial features were often not reported (not reported: nonconcurrent control, 61 of 127 [48.0%]; multiplicity adjustment for arms, 98 of 127 [77.2%]; statistical framework, 37 of 127 [29.1%]). Adaptive design features were only used by half the studies (63 of 127 [49.6%]). Results were available for 65.2% of closed arms (230 of 353). Premature closure of platform trial arms due to recruitment problems was infrequent (5 of 353 [1.4%]).
CONCLUSIONS AND RELEVANCE
This systematic review found that platform trials were initiated most frequently during the COVID-19 pandemic and declined thereafter. The reporting of platform features and the availability of results were insufficient. Premature arm closure for poor recruitment was rare.
Topics: Humans; Pandemics; COVID-19; Cognition; Data Accuracy; Medical Oncology
PubMed: 38506807
DOI: 10.1001/jamanetworkopen.2024.3109 -
Archives of Physiotherapy 2024Manual therapy is an often-utilized intervention for the management of knee osteoarthritis (OA). The interpretation of results presented by these trials can be affected... (Review)
Review
INTRODUCTION
Manual therapy is an often-utilized intervention for the management of knee osteoarthritis (OA). The interpretation of results presented by these trials can be affected by how well the study designs align applicability to real-world clinical settings.
AIM
To examine the existing body of clinical trials investigating manual therapy for knee OA to determine where they fall on the efficacy-effectiveness spectrum.
METHODS
This systematic review has been guided and informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Randomized controlled trials that investigated manual therapy treatments for adults with knee OA were retrieved via searches of multiple databases to identify trials published prior to April 2023. The Rating of Included Trials on the Efficacy-Effectiveness Spectrum (RITES) tool was used to objectively rate the efficacy-effectiveness nature of each trial design. The Cochrane Risk of Bias 2.0 assessment tool (RoB-2) was used to assess the risk of bias across five domains.
RESULTS
Of the 36 trials, a higher percentage of trials had a greater emphasis on efficacy within all four domains: participant characteristics (75.0%), trial setting (77.8%), flexibility of intervention (58.3%), and clinical relevance of experimental and comparison intervention (47.2%). In addition, 13.9% of the trials had low risk of bias, 41.7% had high risk of bias, and 44.4% had some concerns regarding bias.
CONCLUSIONS
While many trials support manual therapy as effective for the management of knee OA, a greater focus on study designs with an emphasis on effectiveness would improve the applicability and generalizability of future trials.
PubMed: 38444787
DOI: 10.33393/aop.2024.2916 -
Orphanet Journal of Rare Diseases Feb 2024Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA...
BACKGROUND
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. Late-infantile, juvenile and adult clinical subtypes are defined by symptom onset at ≤ 2.5, > 2.5 to < 16 and ≥ 16 years, respectively. Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug.
METHODS
To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. Where possible, results were stratified by clinical subtype. Data were extracted from non-interventional studies (clinical trials, non-clinical studies and case reports were excluded; reviews were used for snowballing only).
RESULTS
Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia-Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal). In the three European studies with estimates stratified by clinical subtypes, birth prevalence was highest for late-infantile cases (0.31-1.12 per 100,000 live births). The distribution of clinical subtypes reported in cases diagnosed over various time periods in 17 studies varied substantially, but late-infantile and juvenile MLD accounted for at least two-thirds of cases in most studies.
CONCLUSIONS
This review provides a foundation for further analysis of the regional epidemiology of MLD. Data gaps indicate the need for better global coverage, increased use of epidemiological measures (e.g. prevalence estimates) and more stratification of outcomes by clinical and genetic disease subtype.
Topics: Adult; Humans; Cerebroside-Sulfatase; Europe; Leukodystrophy, Metachromatic; Lysosomal Storage Diseases; Prevalence
PubMed: 38383398
DOI: 10.1186/s13023-024-03044-w -
Obesity Reviews : An Official Journal... May 2024Consideration of how applicable the results of surgical trials are to clinical practice is important to inform decision-making. Randomized controlled trials comparing at... (Review)
Review
Randomized controlled trials comparing gastric bypass, gastric band, and sleeve gastrectomy: A systematic review examining validity and applicability to wider clinical practice.
Consideration of how applicable the results of surgical trials are to clinical practice is important to inform decision-making. Randomized controlled trials comparing at least two surgical interventions (of gastric bypass, gastric band, and sleeve gastrectomy) for severe and complex obesity were examined using the PRagmatic Explanatory Continuum Indicator Summary-2 tool, to consider how applicable the trial results are to clinical practice, and the Risk of Bias 2 tool, to examine validity. MEDLINE, Embase, and CENTRAL databases were searched for studies published between November 2013 and June 2021, and 15 were identified. Using the PRagmatic Explanatory Continuum Indicator Summary-2 tool, three were classified as pragmatic, with good applicability to clinical practice. Ten had more explanatory domains but did include some pragmatic characteristics, and two were predominantly explanatory. This was due to some trial design features that would not be considered applicable to the wider clinical setting, including being single-centered, having prescribed intervention delivery methods, and intensive follow-up regimens. Only two trials had low risk of bias, of which one was considered pragmatic. Three had high risk of bias. Overall, few trials in bariatric surgery are pragmatic with low risk of bias. Well-designed pragmatic trials are needed to inform practice and reduce research waste.
Topics: Humans; Gastric Bypass; Research Design; Randomized Controlled Trials as Topic; Obesity; Gastrectomy
PubMed: 38346786
DOI: 10.1111/obr.13718 -
Health Technology Assessment... Jan 2024Up to 30% of children have constipation at some stage in their life. Although often short-lived, in one-third of children it progresses to chronic functional...
BACKGROUND
Up to 30% of children have constipation at some stage in their life. Although often short-lived, in one-third of children it progresses to chronic functional constipation, potentially with overflow incontinence. Optimal management strategies remain unclear.
OBJECTIVE
To determine the most effective interventions, and combinations and sequences of interventions, for childhood chronic functional constipation, and understand how they can best be implemented.
METHODS
Key stakeholders, comprising two parents of children with chronic functional constipation, two adults who experienced childhood chronic functional constipation and four health professional/continence experts, contributed throughout the research. We conducted pragmatic mixed-method reviews. For all reviews, included studies focused on any interventions/strategies, delivered in any setting, to improve any outcomes in children (0-18 years) with a clinical diagnosis of chronic functional constipation (excluding studies of diagnosis/assessment) included. Dual reviewers applied inclusion criteria and assessed risk of bias. One reviewer extracted data, checked by a second reviewer. We systematically searched electronic databases (including Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature) (January 2011 to March 2020) and grey literature, including studies (any design) reporting any intervention/strategy. Data were coded, tabulated and mapped. Research quality was not evaluated. For each different intervention, we included existing systematic reviews judged to be low risk of bias (using the Risk of Bias Assessment Tool for Systematic Reviews), updating any meta-analyses with new randomised controlled trials. Where there was no existing low risk of bias systematic reviews, we included randomised controlled trials and other primary studies. The risk of bias was judged using design-specific tools. Evidence was synthesised narratively, and a process of considered judgement was used to judge certainty in the evidence as high, moderate, low, very low or insufficient evidence. Included studies (any design, English-language) detailed intervention-related costs. Studies were categorised as cost-consequence, cost-effectiveness, cost-utility or cost-benefit, and reporting quality evaluated using the consensus health economic criteria checklist. Included studies reported data relating to implementation barriers or facilitators. Using a best-fit framework synthesis approach, factors were synthesised around the consolidated framework for implementation research domains.
RESULTS
Stakeholders prioritised outcomes, developed a model which informed evidence synthesis and identified evidence gaps.
SCOPING REVIEW
651 studies, including 190 randomised controlled trials and 236 primary studies, conservatively reported 48 interventions/intervention combinations.
EFFECTIVENESS SYSTEMATIC REVIEWS
studies explored service delivery models ( = 15); interventions delivered by families/carers ( = 32), wider children's workforce ( = 21), continence teams ( = 31) and specialist consultant-led teams ( = 42); complementary therapies ( = 15); and psychosocial interventions ( = 4). One intervention (probiotics) had moderate-quality evidence; all others had low to very-low-quality evidence. Thirty-one studies reported evidence relating to cost or resource use; data were insufficient to support generalisable conclusions. One hundred and six studies described implementation barriers and facilitators.
CONCLUSIONS
Management of childhood chronic functional constipation is complex. The available evidence remains limited, with small, poorly conducted and reported studies. Many evidence gaps were identified. Treatment recommendations within current clinical guidelines remain largely unchanged, but there is a need for research to move away from considering effectiveness of single interventions. Clinical care and future studies must consider the individual characteristics of children.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42019159008.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 128470) and is published in full in ; Vol. 28, No. 5. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Humans; Systematic Reviews as Topic; Health Personnel; Constipation
PubMed: 38343084
DOI: 10.3310/PLTR9622 -
International Journal of Medical... Apr 2024Emergency department overcrowding could be improved by upstream telephone triage. Emergency telephone triage aims at managing and orientating adequately patients as... (Review)
Review
OBJECTIVES
Emergency department overcrowding could be improved by upstream telephone triage. Emergency telephone triage aims at managing and orientating adequately patients as early as possible and distributing limited supply of staff and materials. This complex task could be improved with the use of Clinical decision support systems (CDSS). The aim of this scoping review was to identify literature gaps for the future development and evaluation of CDSS for Emergency telephone triage.
MATERIALS AND METHODS
We present here a scoping review of CDSS designed for emergency telephone triage, and compared them in terms of functional characteristics, technical design, health care implementation and methodologies used for evaluation, following the PRISMA-ScR guidelines.
RESULTS
Regarding design, 19 CDSS were retrieved: 12 were knowledge based CDSS (decisional algorithms built according to guidelines or clinical expertise) and 7 were data driven (statistical, machine learning, or deep learning models). Most of them aimed at assisting nurses or non-medical staff by providing patient orientation and/or severity/priority assessment. Eleven were implemented in real life, and only three were connected to the Electronic Health Record. Regarding evaluation, CDSS were assessed through various aspects: intrinsic characteristics, impact on clinical practice or user apprehension. Only one pragmatic trial and one randomized controlled trial were conducted.
CONCLUSION
This review highlights the potential of a hybrid system, user tailored, flexible, connected to the electronic health record, which could work with oral, video and digital data; and the need to evaluate CDSS on intrinsic characteristics and impact on clinical practice, iteratively at each distinct stage of the IT lifecycle.
Topics: Humans; Triage; Decision Support Systems, Clinical; Delivery of Health Care; Emergency Service, Hospital; Telephone
PubMed: 38290244
DOI: 10.1016/j.ijmedinf.2024.105347